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Anatomy and projection patterns of the superior olivary complex in the Mexican free-tailed bat, Tadarida brasiliensis mexicana.

The superior olivary complex (SOC) is the first station in the ascending auditory pathway that receives binaural projections. Two of the principal nuclei, the lateral superior olive (LSO) and the medial superior olive (MSO), are major sources of ascending projections to the inferior colliculus. Whereas almost all mammals have an LSO, it has traditionally been thought that only animals that hear low frequencies have an MSO. Recent reports, however, suggest that the medial part of the SOC in bats is highly variable and that at least some bats have a well-developed MSO. Thus, the main goal of this study was to evaluate the cytoarchitecture and connections of the principal superior olivary nuclei of the Mexican free-tailed bat, with specific attention directed at the MSO. Cell and fiber stained material revealed that the LSO and the medial nucleus of the trapezoid body (MNTB) are similar to those described for other mammals. There are two medial nuclei we refer to as dorsomedial periolivary nucleus (DMPO) and MSO. Tracer experiments exhibited that the DMPO receives bilateral projections from the cochlear nucleus, and additional projections from the ipsilateral MNTB. The DMPO sends a strong projection to the ipsilateral inferior colliculus. Positive staining for acetylcholinesterase indicates that the DMPO is a part of the olivocochlear system, as it is in other animals. The MSO in the free-tailed bat meets many of the criteria that traditionally define this nucleus. These include the presence of bipolar and multipolar principal cells, bilateral innervation from the cochlear nucleus, a strong projection from the ipsilateral MNTB, and the absence of cholinergic cells. The major difference from traditional MSO features is that it projects bilaterally to the inferior colliculus. Approximately 30% of its cells provide collateral projections to the colliculi on both sides. Functional implications of the MSO for the free-tailed bat are considered in the Discussion.

Acetylcholinesterase↗

Speech perception as a function of electrical stimulation rate: using the Nucleus 24 cochlear implant system.

OBJECTIVE: To investigate the effect of varying electrical stimulation rate on speech comprehension by cochlear implant users, while keeping the number of stimulated channels constant. DESIGN: Three average rates of electrical stimulation, 250, 807, and 1615 pulses per second per channel (pps/ch), were compared using a speech processing strategy that employed an electrode selection technique similar to that used in the Spectral Maxima Sound Processor strategy (McDermott, McKay, & Vandali, 1992; McDermott & Vandali, Reference Note 1; McKay, McDermott, Vandali, & Clark, 1991) and the Spectral Peak strategy (Skinner et al., 1994; Whitford et al., 1995). Speech perception tests with five users of the Nucleus 24 cochlear implant system were conducted over a 21-wk period. Subjects were given take-home experience with each rate condition. A repeated ABC evaluation protocol with alternating order was employed so as to account for learning effects and to minimize order effects. Perception of open-set monosyllabic words in quiet and open-set sentences at signal to noise ratios ranging from +20 to 0 dB, depending on the subject's ability, were tested. A comparative performance questionnaire was also administered. RESULTS: No statistical differences in group performance between the 250 and 807 pps/ch rates were observed in any of the speech perception tests. However, significantly poorer group performance was observed for the 1615 pps/ch rate for some tests due predominantly to the results of one subject. Analysis of individual scores showed considerable variation across subjects. For some subjects, one or more of the three rate conditions evaluated provided benefits on some speech perception tasks. The results of the comparative performance questionnaire indicated a preference for the 250 and 807 pps/ch rates over the 1615 pps/ch rate for most listening situations. CONCLUSIONS: For the speech processing strategy, implant system, and subjects evaluated in this study, the group results indicated that the use of electrical stimulation rates higher than 250 pps/ch (up to 1615 pps/ch) generally provided no significant improvement to speech comprehension. However, individual results indicated that perceptual benefits could be obtained by adjusting rate of stimulation optimally to suit each subject. Results from one subject, together with tinnitus problems arising from high-rate stimulation for another subject, indicated that high rates of stimulation may in fact be undesirable for some subjects.

Adult↗

Responses from the brainstem at the entrance of the eighth nerve in human to contralateral stimulation.

Recordings were made from the exposed eighth nerve (N VIII) and the lateral brainstem near the root entry zone of N VIII to contralateral click stimulation in patients undergoing microvascular decompression operations to relieve hemifacial spasm or trigeminal neuralgia. Similar recordings were made in patients undergoing operations to remove acoustic tumors using a retromastoid approach to the cerebellopontine angle. The waveform of the response that was recorded using a monopolar electrode placed on the intracranial portion of the eighth nerve was similar to the potentials recorded from the lateral surface of the brainstem near the entrance of the eighth nerve, and consisted of a positive deflection with a latency of about 4 ms, and sometimes a second and smaller positive peak with a slightly shorter latency than that of peak V in the BAEP could be seen in such recordings. It was concluded that the potentials are generated in brainstem structures, most likely the cochlear nucleus. It is assumed that when the potentials are recorded from the exposed eighth nerve, the nerve passively conducts the activity from the active structure to the recording site. The latency of the main positive peak in these potentials does not bear any direct relationship to any identifiable component of the farfield evoked potentials when these potentials are recorded from the vertex or the earlobe of the stimulated ear and a noncephalic reference is used. It seems likely that the potential is generated by fibers that originate in cells in the cochlear nucleus on the stimulated side, and that the initial positivity reflects the termination of these fibers in the cochlear nucleus on the side from which the recording is made.

Brain Stem↗

Double-pulse stimulation of startle-like responses in rats: refractory periods and temporal summation.

A startle-like response was evoked by electrical stimulation with one pulse in several brainstem sites of the primary acoustic startle circuit. If a second pulse was delivered 0.4-10 ms after the first pulse, a stronger response or a decreased current threshold resulted. The facilitatory effect of the second pulse increased as interpulse (C-T) interval increased from 0.4 to 2.0 ms in cochlear nucleus or ventral lateral lemniscus sites. In caudal pontine reticular formation sites, the effect of the second pulse increased sharply from 0.3 to 0.5 ms. These results suggest that very short refractory period axons mediate electrically elicited startle in reticular formation, and that longer refractory period axons mediate startle in cochlear nucleus or ventral lateral lemniscus. In reticular formation sites, the effect of the second pulse declined nearly exponentially from 2.0 to 50 ms with a time constant of about 4 ms. Stimulation of similar reticular formation sites in cats evokes monosynaptic EPSPs in spinal motoneurons with an almost identical time course, as reported by other investigators. This suggests that the startle response evoked from the reticular formation results from monosynaptic activation of spinal motoneurons. Temporal summation declined more slowly and irregularly in cochlear nucleus and ventral lateral lemniscus sites, suggesting that these sites are not monosynaptically connected with spinal motoneurons, a conclusion consistent with anatomical data. In reticular formation sites near the facial nerve, a second peak in the two-pulse curve was observed at a C-T interval of 10 ms. The second peak was blocked by local anesthesia of the face ipsilateral to the stimulating electrode, suggesting that a single twitch of facial muscles facilitates startle.

Action Potentials↗

Functional/metabolic modulation of the brain stem lesions caused by 1,3-dinitrobenzene in the rat.

To determine whether neuronal activity plays a role in the localisation of brain stem lesions in 1,3-dinitrobenzene intoxication we produced asymmetrical changes in auditory input by rupturing the left tympanic membrane in Fischer rats. This raised the auditory threshold on that side from 57-63 dB to 104-122 dB. It also decreased glucose utilisation in the ipsilateral cochlear nucleus and significantly increased utilisation in the contralateral nucleus, resulting in a relative deficit of 72 +/- 6%. Similarly, tympanic membrane rupture led to decreased glucose utilisation in the contralateral and increased utilisation in the ipsilateral inferior colliculus. Additional exposure to "white noise" prevented the decrease in glucose utilisation in the contralateral inferior colliculus. Dosing with dinitrobenzene (10 mg/kg in 4 doses over 48 hr) to otherwise normal rats produces symmetrical vasculonecrotic lesions in these regions, but in animals with left tympanic membrane rupture the severity of morphological changes in the ipsilateral cochlear nucleus and the contralateral inferior colliculus were substantially reduced. Additional exposure to "white noise" increased the degree of damage in the ipsilateral cochlear nucleus and contralateral inferior colliculus. These findings indicate that altered auditory function in rats, with its associated metabolic consequences exercises a significant role in the development of brain stem damage in auditory pathways following dinitrobenzene intoxication.

Acoustic Stimulation↗

A primary acoustic startle circuit: lesion and stimulation studies.

The latency of the acoustic startle reflex in the rat is 8 msec, measured from tone onset to the beginning of the electromyographic response in the hindleg. This extremely short latency indicates that only a few synapses could be involved in some primary acoustic startle circuit. Acoustic startle is being used as a model system for studying habituation, sensitization, prepulse inhibition, classical conditioning, fear or anxiety, and drug effects on behavior. The present study attempted to delineate a short latency acoustic startle circuit, since this would provide critical information for further study in all of these areas. Bilateral lesions of the ventral cochlear nucleus, which receives the primary auditory input, abolish acoustic startle. Electrical, single pulse stimulation of the ventral cochlear nucleus elicits startle-like responses with a latency of about 7 msec. Bilateral lesions of the dorsal and ventral nuclei of the lateral lemniscus, which receive direct input from the ventral cochlear nuclei, abolish acoustic startle. Electrical stimulation of these nuclei elicits startle-like responses with a latency of about 6 msec. Bilateral lesions of ventral regions of the nucleus reticularis pontis caudalis, which contain cell bodies that give rise to the reticulospinal tract, abolish acoustic startle. Electrical stimulation of these points elicits startle-like responses with a latency of about 5 msec. Reaction product from horseradish peroxidase iontophoresed into this area is found in the nuclei of the lateral lemniscus. In contrast, lesions of the dorsal cochlear nuclei, vestibular nuclei, nucleus reticularis pontis oralis, nucleus reticularis gigantocellularis, and dorsal regions of the nucleus reticularis pontis caudalis fail to abolish acoustic startle. Also, "startle" cannot be elicited electrically from these areas. The data suggest that a primary acoustic startle circuit in the rat consists of auditory nerve, ventral cochlear nucleus, nuclei of the lateral lemniscus, nucleus reticularis pontis caudalis, spinal interneuron, lower motor neuron, and muscles. Hence, five synapses, plus the neuromuscular junction, are probably involved.

Acoustic Stimulation↗

Topographic organization of the central projections of the spiral ganglion in cats.

The morphological organization of inputs from restricted sectors of the cat cochlear spiral ganglion into the cochlear nucleus was studied by making focal extracellular injections of horseradish peroxidase (HRP) into the spiral ganglion. Injections resulted in Golgi-like labeling of a small cluster of spiral ganglion cells and their peripheral and central axons. Large injections involved most of the cells within Rosenthal's canal in sectors of the spiral ganglion innervating greater than or equal to 1 mm of the basilar membrane and resulted in narrow, complete laminae of labeled axons and preterminal fields within each cochlear nucleus subdivision. The positions of these bands were consistent with the "isofrequency laminae" appropriate for the frequencies represented at the injection sites, with high frequency laminae situated more dorsally, and lower frequencies progressively more ventral. A discrete projection to the small cell cap area was observed that was discontinuous with the main projection laminae in the ventral cochlear nuclei (VCN). In the dorsal cochlear nucleus, projecting fibers and terminals were excluded from the molecular cell layer. No labeled fibers entered the granule cell areas. In contrast to larger injections, very small HRP deposits labeled only part of an isofrequency lamina. Specifically, injections restricted to the scala tympani aspect of the spiral ganglion labeled only the lateral part of VCN isofrequency laminae, whereas injections limited to the scala vestibuli aspect of the ganglion labeled the medial aspect of the isofrequency planes. Thus these data indicate a previously unrecognized topographic representation of the vertical dimension of the spiral ganglion across VCN isofrequency laminae. Some possible functional implications of this projection organization are discussed.

Animals↗

K(+) currents produce P(1) in the RW CAP: evidence from DC current bias, K(+) channel blockade and recordings from cochlea and brainstem.

Tone-burst-evoked compound action potentials (CAP) from the guinea pig round window (RW) are altered by DC current injection through the RW. The CAP waveform consists of a series of interleaved negative and positive peaks (N(1), P(1), N(2), P(2) etc.) of decreasing amplitude. During positive DC current injection (around +50 microA) the positive peaks are depressed substantially and there is an overall negative baseline shift of the waveform following the N(1). Negative current injection (around -50 microA) increased the positive peaks, in particular P(1), and produced an overall positive baseline shift following the N(1) peak. Results support our hypothesis that the first and dominant N(1) peak in the RW CAP is due to depolarising Na(+) currents into the primary afferent dendrites and axons within the cochlea, and that the P(1) potential is largely due to the exit of the hyperpolarising K(+) currents in the same cells. We have reached this conclusion on the basis of the sign and latency of the N(1) and P(1) components at the RW, beneath the myelin layers around the spiral ganglion cells, at the internal auditory meatus (IAM) within the brain case, and on the basis of the differential susceptibility of the various peaks to perfusion of lidocaine in the cochlear nucleus, sectioning of the cochlear nerve at the IAM, application of the K(+) channel blockers 4-amino-pyridine and tetraethylammonium within the cochlea, and DC current biasing at the RW.

4-Aminopyridine↗

A biphasic change in ribosomal conformation during transneuronal degeneration is altered by inhibition of mitochondrial, but not cytoplasmic protein synthesis.

Following loss of eighth nerve input, 20-40% of neurons in the neonatal chick cochlear nucleus, nucleus magnocellularis (NM), undergo cell death. Intracellular changes that precede the death of NM neurons include increased oxidative metabolism and mitochondrial volume, decreased cytoplasmic protein synthesis, and destruction of ribosomes. Six hours following afferent deprivation, dying NM neurons demonstrate complete loss of ribosomes and cessation of protein synthesis, suggesting that the rapid destruction of ribosomes leads to neuronal death. Increased NM neuron death occurs when mitochondrial upregulation is prevented by chloramphenicol, a mitochondrial protein synthesis inhibitor. This finding suggests that increased oxidative capacity is required for neuronal survival following loss of afferent input. To study changes in the ribosomes of afferent-deprived NM neurons, we obtained a monoclonal antibody to ribosomal RNA. This monoclonal antibody, Y10B, labels ribosomes of all NM neurons receiving normal synaptic activity. Following removal of afferent input, NM neurons demonstrate a biphasic change in their pattern of Y10B label. During the initial phase, there is a uniform decrease in the density of Y10B label. In the second phase, some NM neurons recover the capacity to bind the Y10B antibody while others remain unlabeled. During this second phase, NM neurons putatively destined to die, based on their failure to synthesize protein, are unlabeled by the Y10B antibody. New gene expression is not necessary to initiate the change in ribosomal immunoreactivity that leads deafferented NM neurons toward cell death. Blocking cytoplasmic protein synthesis with cycloheximide had no effect on the biphasic change in Y10B labeling of afferent-deprived NM neurons. Treating chicks with chloramphenicol, however, prevented the recovery of Y10B immunoreactivity in NM neurons during the second phase of the response to afferent deprivation.

Afferent Pathways↗

The effects of limiting the number of Nucleus 22 cochlear implant electrodes programmed on speech perception.

The purpose of this double-blind study was to evaluate systematically the effects of varying programmed electrodes on speech perception. The performance of five subjects implanted with the Nucleus 22-electrode cochlear implant was compared on the Four-Choice Spondee test, the Central Institute for the Deaf Sentence test, and Speech Tracking across the following conditions: (1) five most apical electrodes eliminated from the subject's MAP (stimulus parameters); (2) five most basal electrodes eliminated from subject's MAP; (3) the middle five electrodes eliminated from subject's MAP; and (4) subject's current MAP. Statistically significant differences were found for the Four-Choice Spondee test and both the auditory-only and auditory-plus-lipreading Speech Tracking measures. Three subjects demonstrated poorer performance on all test measures when the five electrodes from the apical portion of the array were not programmed. Two subjects performed equally well, regardless of MAP condition. Group means for all test measures present a trend of consistently poorer performance when the -5 Apex MAPs were utilized. A subjective rating scale was consistent with the perceptual tests, with all subjects best liking their current MAP and least liking the -5 Apex MAP. Results suggest that for some subjects, a fixed place code may control their ability to use spectral information for speech discrimination. For these subjects, first formant information (F1) traditionally coded on the most apical electrodes could not be utilized as effectively when coded on the adjacent middle electrodes.

Acoustic Stimulation↗

Pharmacology of excitatory amino acid neurotransmission in nucleus laminaris of the chick.

The receptors mediating excitatory neurotransmission from the cochlear nucleus (nuc. magnocellularis, NM) to third-order auditory neurons in nucleus laminaris (NL) of the chicken were studied using in vitro brain slices, bath application of drugs, and electrophysiological recording of postsynaptic field potentials. Postsynaptic responses in NL were blocked completely, in a concentration-dependent and reversible fashion, by bath application of the broad-spectrum excitatory amino acid (EAA) antagonist kynurenic acid, the 'non-NMDA' EAA receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX), and the EAA agonists domoic acid, kainic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and quisqualic acid. The selective NMDA receptor antagonists 3-[-)-2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP) and dibenzocycloheptenimine (MK-801) had no effect. The results demonstrate that excitatory input from the cochlear nucleus to NL is mediated by non-NMDA (G2) EAA receptors which exhibit some of the pharmacologic features typical of the AMPA receptors defined by binding studies.

Amino Acids↗

[An experimental study of the auditory brainstem implant in guinea pigs].

In order to examine the characteristics of the auditory brainstem implant, an animal model with electrical stimulation of the cochlear nucleus in guinea pigs was created. Middle latency response (MLR) to pulsatile electrical stimulation of the cochlear nucleus was recorded from the auditory cortex with bipolar plantinumiridium electrodes and stereotaxic technique. The electrically and acoustically generated MLRs have a similar morphology though there are little differences in the latencies, wave intervals and dynamic ranges. The results indicated that the central auditory pathways can be activated by means of electrical stimulation. The safety of the brain tissue to the electrical stimulation are also discussed.

Acoustic Stimulation↗

Brainstem auditory pathway degeneration associated with chronic cochlear implants in the monkey.

The form and pattern of first-order and transsynaptic degeneration in the central auditory pathway was studied in monkeys following inner ear stimulation by a cochlear implant. Multielectrode, scala tympani, and modiolar systems were implanted; in some cases, neomycin was perfused into the cochlea to destroy the organ of Corti at the time of implantation. The monkeys were maintained chronically for 5 to 120 weeks, then the cochleas and brainstems were examined histologically. The extent of spiral ganglion cell loss across animals showed variability, reflecting the different procedures and devices used. The degree and distribution of spiral ganglion cell loss was related to the degree and distribution of neural degeneration seen in the cochlear nucleus in all cases. Peripheral damage progressed toward the cochlear apex as survival time increased, and this progression was reflected in the cochlear nucleus by a ventrolateral shift in the locus of degeneration over time. In addition, evidence for transneuronal degeneration was seen at the superior olive, the lateral lemniscus and the inferior colliculus. Our findings indicate that several factors inherent in the use of a cochlear prosthesis, i.e., insertion trauma, host reaction, and/or electrical stimulation, may be associated with a long-term, continuing process of central degeneration visible at several levels of the auditory system.

Animals↗

Auditory brainstem implantation: the University of Verona experience.

OBJECTIVE: We sought to describe the advantages of the retrosigmoid-transmeatal (RS-TM) approach in the application of auditory brainstem implants (ABIs) in adults with monolateral and bilateral vestibular schwannoma (VS) and in children with cochlear nerve aplasia. STUDY DESIGN: We conducted a retrospective case review. SETTING: The study was conducted at the ENT Department of the University of Verona, Italy. PATIENTS: Six adult patients (5 men and 1 woman) with neurofibromatosis type 2 (NF2) were operated on for VS removal with ABI. An additional patient had a unilateral VS in the only hearing ear. Tumor size ranged from 12 to 40 mm. In addition, 2 children received ABIs for bilateral cochlear nerve aplasia. INTERVENTION: An RS-TM approach was used in all VS patients, and an RS approach was used in the subjects with cochlear nerve aplasia. After tumor excision, landmarks (VII, VIII and IX cranial nerves, choroid plexus) for the foramen of Luschka were carefully identified. The choroid plexus was then partially removed and the tela choroidea divided and bent back; the floor of the lateral recess of the fourth ventricle and the convolution of the dorsal cochlear nucleus became visible. In the 2 subjects with no cochlear nerve, the choroid plexus and VII and IX cranial nerves were used as landmarks. The electrode array was then inserted into the lateral recess and the correct position was monitored with the aid of electrically evoked auditory brainstem responses (EABR) and neural response telemetry (NRT). RESULTS: Correct implantation was possible in all patients. Auditory sensations were induced in all patients with various numbers of electrodes. Different pitch sensations could be identified with different electrode stimulation. CONCLUSIONS: We believe that the RS approach is the route of choice for patients who are candidates for ABI due to the easy and clear access to the cochlear nucleus area. This route avoids some of the drawbacks of the translabyrinthine approach, such as mastoidectomy, labyrinthectomy, sealing of the cavity and posterior fossa with abdominal fat, and contamination from the middle ear. For this reason, it is the route of choice in children with cochlear nerve aplasia or severe cochlear malformation and in adults with complete ossification of the cochlea or cochlear nerve disruption due to cranial trauma.

Acoustic Stimulation↗

Effects of early deafness on development of brain stem auditory neurons.

Early destruction of the otocyst (embryonic precursor of the inner ear) in chick embryos results in complex changes in developing central auditory pathways. In the cochlear nucleus angularis (NA) and nucleus magnocellularis (NM), 30% to 40% of the neurons die after otocyst removal, the survivors are shrunken, and some neurons in the NA migrate to an abnormal position in the brain stem. The characteristic forms of cochlear nucleus neurons develop normally in the absence of cochlear nerve input, however. In the nucleus laminaris (NL), development of normal dendritic size is dependent on a normal inner ear, but most of the highly specialized dendritic organization of this nucleus, which is important for low-frequency sound localization, can develop normally in the absence of cochlear influences. Otocyst removal induces formation of a permanent functional aberrant axonal projection to the ipsilateral NM from the contralateral NM. Although these aberrant axons form functional glutamatergic synapses, these show immature functional properties, suggesting that cochlear nerve inputs are necessary for normal maturation of glutamate receptors on auditory neurons. Treatment of chick embryo for a brief period in ovo with 6-cyano-7-nitroquinoxaline-2,3-dione, a quinoxalinedione antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-kainate subtype of glutamate receptor, completely and permanently prevents the neuronal loss in the NM produced by otocyst removal. The work reviewed has 1) identified aspects of development in central auditory neurons that are perturbed by profound early sensorineural loss, 2) identified aspects of development that appear independent of cochlear influences, and 3) suggested a potential chemotherapeutic approach to prevention of central neuronal death after early damage to the cochlea.

Animals↗

Intracellular labeling of afferents to the lateral superior olive in the bat, Eptesicus fuscus.

An in vitro tissue slice preparation of the bat brain stem was used to label intracellularly individual axons projecting to the lateral superior olive from two different sources: the medial nucleus of the trapezoid body (MNTB) and the anteroventral cochlear nucleus (AVCN). The tracing of individually labeled MNTB axons into the lateral superior olive reaffirms the long accepted indirect route by which information from the contralateral ear reaches the lateral superior olive. While the MNTB appears to relay input from the contralateral AVCN, information from the ipsilateral ear reaches the lateral superior olive via a direct projection from the ipsilateral AVCN. Axons from the contralateral and ipsilateral pathways have different distribution patterns upon the fusiform cells of the lateral superior olive. Axon terminals of MNTB principal cells have a perisomatic and proximal dendritic distribution pattern. Axon terminal varicosities from the ipsilateral anteroventral cochlear nucleus are distributed primarily to more distal dendrites.

Animals↗

Polystyrene microplastics induce auditory neurotoxicity in mammals: Integrated multi-omics profiling reveals oxidative damage and synaptic molecular dysregulation.

Microplastics (MPs) are ubiquitous environmental pollutants, yet their neurotoxic effects on the auditory system remain poorly understood. This study develops an integrated multi-level analytical framework combining auditory neurophysiology, behavioral assessment, tissue biochemistry, transcriptomics, and proteomics to investigate polystyrene (PS)-MPs-induced auditory neurotoxicity in rats. PS-MPs infiltrate the auditory system and significantly impair auditory processing, with central dysfunction emerging earlier and more prominently than peripheral alterations. Multi-omics analyses reveal coordinated suppression of glutamatergic synapse and Wnt signaling pathways in the cochlear nucleus. Mechanistically, PS-MPs perturb the crosstalk between glutamatergic synaptic and Wnt signaling, promoting AMPA receptor (AMPAR) internalization and potentially affecting synaptic plasticity-related processes and neuronal responsiveness. In parallel, PS-MPs trigger oxidative stress, apoptosis, and glial activation, reflecting pronounced neuroinflammatory and redox imbalance. In primary cochlear nucleus neurons (PCNNs), these mechanisms were further validated in vitro, where activation of Wnt signaling by Wnt3a significantly alleviated oxidative injury and reduced AMPAR internalization. Collectively, these findings provide comprehensive preclinical evidence for the neurotoxic potential of MPs and reveal a previously unrecognized PS-MPs-induced auditory neurotoxicity, although further studies are needed for human relevance. Results from the rat model further implicate Wnt-mediated signaling as a potential modulatory pathway underlying MPs-induced synaptic molecular alterations and redox dysfunction.

Animals↗

Oxytocin within auditory nuclei: a neuromodulatory function in sensory processing?

Oxytocin (OT) plays an important role in social bonding, ultrasonic vocalizations and other sexual behaviors in mammalian species. Although its presence within neuroendocrine regions in the forebrain is well established, its association with sensory nuclei remains unclear. We report here the presence of oxytocin immunoreactive neurons within several nuclei in the auditory brain stem of the mustached bat, Pteronotus parnellii. Immunocytochemical procedures revealed OT-immunoreactive perikarya and/or fiber terminals in restricted areas of the inferior colliculus (IC), superior olivary complex (SOC), including the medial and ventral nuclei of the trapezoid body, and in the cochlear nucleus. Perikarya were labeled predominantly in the IC and SOC and both perikarya and fiber terminals were labeled extensively in the cochlear nucleus.

Animals↗